Endemic (Balkan) nephropathy (EN) is a chronic tubulointerstitial nephropathy frequently associated with upper urothelial cancer exclusively affecting farming villagers [1,2,3]. Based on our results, EN is considered to be an environmental form of aristolochic acid nephropathy (AAN) [1,2.3]. AAN was first reported in 1993 in Belgium and subsequently more AAN cases were reported worldwide as AA has been an integral part of traditional herbal medicines [4]. The extent of this problem was recently documented in Taiwan where precise data on prescriptions of herbal products containing AA is available [5]. Aristolochia spp. has been used for more than 2000 years in the practice of traditional medicine and European physicians were familiar with the use of this plant as well. After its intrinsic toxicity became known, importing Aristolochia herbs was banned in many countries, including Croatia. Nevertheless, products containing AA remain a part of traditional medicine and are sold in many countries that do not have strict control protocols. Recently we reported that AA DNA adducts were present in 95% of patients with EN who underwent surgery for upper urothelial cancers [2] and affirmed the idea that bread contaminated with AA might be the cause of EN [6,7]. However, the causative relationship between AA and EN again raised the question whether bread intake is the only route of ingestion or whether AA was ingested also in EN as a part of folkloric medicine. Gluhovschi et al. reported that although therapeutic remedies based on AA products are used in the EN affected area, no relationship between these remedies and the development of EN or of tumors was observed [8]. However, they used HPLC for detection of AA in plasma, which is less sensitive than the mass spectrometry we recently used [1,2]. In addition, when re-analyzing their data, it does appear that AA was used more frequently in the endemic area. In our opinion, this leaves the question whether herbal tea may play a role in EN still unanswered. In our preliminary study we failed to find any evidence in the group of 1041 Croatian farmers that herbal tea or traditional medicine use is related to EN [9]. The observed differences between Romania and Croatia might reflect cultural and historical differences in traditional medicine. Aiming to resolve this disagreement more conclusively we analyzed whether herbal teas, including those prepared from Aristolochia clematitis, were used more frequently in Croatian and Bosnian residents of an endemic area than in farmers from non-endemic villages. A total of 3168 adults from nine endemic and three non-endemic villages were enrolled (the participation rate was 76.73%). The epidemiological survey was designed to collect demographic, medical, and family history information, as well as dietary and environmental exposures, with an emphasis on the exposure to AA through drinking teas prepared from A. clematitis. Farmers were asked questions: 1): Did you ever use any herbal teas when you were sick?; 2): Did you ever buy, prepare or...
Objective:Hepatocyte growth factor (HGF) is a pleiotropic factor that regulates cellular processes such as cell survival, proliferation, migration, and differentiation. Serum HGF concentration is associated with systolic blood pressure (BP) and is higher in hypertensive than in normotensive individuals, especially if complications of arterial hypertension are developed. Our aim was to determine the association of serum HGF concentration in subjects with prehypertension.Design and method:Data from 612 subjects (57,8% women, average age 41 years) was nalysed. After clinical examination, fasting blood and urine samples were drawn. HGF was measured using a commercial test. BP was measured according to the ESC/ESH guidelines. Based on BP values, subjects were divided into two groups: OBP - subjects with optimal blood pressure (BP < 120/80 mmHg, N = 295), and PHT (subjects with BP 120/80–140/90 mmHg N = 317).Results:Subjects with PHT were significantly older and had higher values of body mass index, waist circumference, serum total cholesterol levels, triglyceride levels, and fasting glucose levels (all p < 0.001). The prevalence of metabolic syndrome was significantly higher in PHT group (4.3% vs. 30.4%, p < 0,001). Serum HGF concentrations were higher in PHT subjects, but the difference was not significant (270.8 vs. 277.9 pg/ml, p = 0.651). Serum HGF concentration showed a significant positive correlation to systolic and diastolic BP in PHT (r = 0,226, p < 0,05 and r = 0,232, p < 0,01, respectively), but not in OBP group (p > 0.05).Conclusions:Serum HGF is associated with BP in prehypertensive subjects, but not in subjects with optimal BP. In our cohort, the correlation is more pronounced for diastolic blood pressure.
Concomitant treatment with drugs that inhibit drug metabolising enzymes and/or transporters, such as commonly prescribed statins and nonsteroidal anti-inflammatory drugs (NSAIDs), has been associated with prolonged drug exposure and increased risk of adverse drug reactions (ADRs) due to drug-drug interactions. The risk is further increased in patients with chronic diseases/comorbidities who are more susceptible because of their genetic setup or external factors. In that light, we present a case of a 46-year-old woman who had been experiencing acute renal and hepatic injury and myalgia over two years of concomitant treatment with diclofenac, atorvastatin, simvastatin/fenofibrate, and several other drugs, including pantoprazole and furosemide. Our pharmacogenomic findings supported the suspicion that ADRs, most notably the multi-organ toxicity experienced by our patient, may be owed to drug-drug-gene interactions and increased bioavailability of the prescribed drugs due to slower detoxification capacity and decreased hepatic and renal elimination. We also discuss the importance of CYP polymorphisms in the biotransformation of endogenous substrates such as arachidonic acid and their modulating role in pathophysiological processes. Yet even though the risks of ADRs related to the above mentioned drugs are substantially evidenced in literature, pre-emptive pharmacogenetic analysis has not yet found its way into common clinical practice.
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